Project Summary: Treatment with radiation or chemo-radiotherapy is the standard therapy for head and neck cancers but this treatment is well known to be less efficacious in patients with hypoxic tumors. Furthermore, cancer therapy may alter tumor physiological status, thus impacting treatment efficacy. Factors that modulate tumor oxygenation include blood flow, blood oxygenation, oxygen metabolism, and nicotine levels (i.e., tobacco use). Tumor hemodynamics and metabolism, however, are not routinely measured during cancer therapy due to the lack of appropriate technologies. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the best currently available and reproducible methods to measure target lesions selected for objective response assessment, but these modalities require large and costly instrumentation that severely limits their routine use in clinics. The capabilities of diffuse optics for continuously monitoring tumor hemodynamics and metabolism during therapy at the clinical bedside have recently been demonstrated in our preliminary studies. The objective of this project is to develop and optimize a noninvasive versatile multi-modality clinical optical instrument to aid in evaluating and predicting tumor responses at the most early stage possible. More specifically, this optical instrument will monitor and predict hemodynamic and metabolic responses to chemo- radiotherapy in head and neck tumors. We hypothesize that functional assessment of tumor physiological status and dynamic changes during therapy will provide information for early prediction of long-term treatment outcomes, thus enabling clinicians to optimize therapy for each patient in a time sensitive fashion. To achieve this goal, we will assemble a hybrid flow and oxygen system that combines a newly developed diffuse correlation spectroscopy (DCS) flowmeter with a commercial tissue-oximeter for simultaneous measurement of tumor blood flow, oxygenation, and oxygen metabolism (derived from the flow and oxygenation data). The instrument including optical probes and a software platform will be tested and optimized for continuous and longitudinal monitoring of tumor physiological status and hemodynamic/metabolic changes before, during and after therapy in patients including smokers and nonsmokers (n=125). It is anticipated that significant correlations will be observed between therapy outcomes (e.g., tumor volume change, tumor toxicity, time to disease recurrence, survival) and tumor physiological status and changes as well as nicotine levels. Different types of physiological parameters may show different sensitivities to cancer therapy in each patient, which could reveal the primary factor(s) affecting individual therapy outcomes. Our novel hybrid optical system will provide hemodynamic and metabolic imaging contrasts complementary to those of CT and MRI, and holds unique potential for early evaluating and predicting cancer therapy responses. Our long-term goal is to develop robust scientific collaborations to optimize and individualize cancer therapy at early stages with noninvasive optical technologies.